Degrees

Biography

Postdoctoral Fellow, University of California, Berkeley, 1985-1989

Research Interests

The principal research effort in my lab is the characterization of the molecular mechanisms of the antifungal drug amiodarone. We were the first to publish work showing amiodarone has potent antifungal activity against a broad spectrum of fungi and we were the first to publish work showing that amiodarone causes a rise in cytoplasmic calcium in response to alteration of the yeast cell wall. Our work is the first showing effects of this drug, caffeine, and cell wall on calcium ion channels in yeast. UNR holds a patent for use of amiodarone as an antifungal based on my research. Published work now shows amiodarone has antiparasitic activity, including an apparent amiodarone cure of a patient with Chagas disease.

In collaboration with Dr. Elizabeth Hejchman, Department of Medical Chemistry, at The Medical University of Warsaw, Poland, we have synthesized compounds related to amiodarone and tested them for antifungal activity and identified novel antifungal compounds.

Perhaps the most famous and industrially important characteristic of the yeast Saccharomyces cerevisiae is its ability to produce ethanol as a metabolic product and to survive high concentrations of this toxic compound. We hypothesized that ethanol should induce a Ca2+ influx analogous to other stresses. We now have data demonstrating a new signaling response elicited by exposure of yeast cells to ethanol, a dramatic rise in the cytoplasmic Ca2+ concentration ([Ca2+]cyt). The ethanol-induced increase in [Ca2+]cyt is largely dependent on the Cch1/Mid1 Ca2+ channel, and affected by cell wall integrity. Our objective is to reveal the functions of the molecular players and physiological conditions involved in this novel signaling process.

Recent research shows that the mainstay antifungal in clinical use for decades, amphotericin B, also causes calcium flux in yeast cells. We have demonstrated synergistic antifungal activity between amiodarone and amphotericin B.